The project will evaluate the structure, function and clinical significance of platelet factor four (PF-4), the heparin neutralizing factor released from platelets during aggregation. PF-4 will be purified from human platelets, labelled with I125, and a radioimmunoassay developed to measure antigenic PF-4. Experiments are planned to: 1) Measure the interaction of PF-4 protein with heparin and other acidicglycosaminoglycans and the effects of specific binding site modifications on this interaction. 2) Observe the effects of PF-4 on platelet aggregation and on the interaction of thrombin and antithrombin. 3) Infuse trace labelled PF-4 into animals and human subjects to evaluate its in vivo half life. 4) Infuse PF-4 into experimental animals to assess its effects on overall hemostasis 5) Determine whether elevations of plasma PF-4 are a good index of intravascular platelet destruction or activation. 6) Correlate the effects of antiplatelet drugs on the patients with accelerated platelet turnover. These studies should help determine whether PF-4 plays an important role in normal hemostasis, or whether its release can be used as a marker for platelet destruction and perhaps to detect intravascular thrombotic events. BIBLIOGRAPHIC REFERENCES: Buchanan, G.R. and Handin, R.I.: Platelet function in the Chediack-Higashi Syndrome. Blood 47:941-948, 1976. Broekman, M.J., Handin, R.I., Derksen, A. and Cohen, P.: Distribution of phospholipids. Fatty acids and platelet factor 3 activity among subcellular fractions of human platelets. Blood 47:963-971, 1976.